FibroGen, announced the publication of positive results from two Phase 2 clinical trials of roxadustat, its therapy candidate for the treatment of anemia in patients with chronic kidney disease (CKD).
The study with the findings, “Phase 2 studies of oral hypoxia-inducible factor prolyl hydroxylase inhibitor FG-4592 for treatment of anemia in China,” was published in the journal Nephrology Dialysis Transplantation.
Anemia is a common complication of CKD, and associated with increased morbidity. Recombinant erythropoiesis-stimulating agents (ESAs) provide improved quality of life in both dialysis and non-dialysis patient groups, and reduce red blood cell (RBC) transfusions.
Roxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl-hydroxylase inhibitor that promotes erythropoiesis by increasing endogenous erythropoietin (the hormone that controls red blood cell production), improving iron regulation and reducing hepcidin, a protein that regulates blood levels of iron. Abnormal levels of hepcidin lead to a decrease in serum iron levels, which subsequently leads to anemia.
Both Phase 2 studies were conducted in China to explore the safety and effectiveness of roxadustat in CKD patients who were dialysis-dependent (DD), and patients who were non-dialysis-dependent (NDD).
In the NDD study, 91 patients were randomly assigned to receive treatment with roxadustat in low (1.1–1.75 mg/kg) or high (1.50–2.25 mg/kg) doses, or to a placebo drug, for eight weeks. Researchers found that after the treatment course hemoglobin (Hb) levels increased by more than 1.0 gm/dL from baseline in 80% of the patients in the low-dose group, and in 87.1% of patients in the high-dose group, compared to 23.3% in placebo-treated patients.
In the DD study, 87 patients who had been treated previously for anemia were assigned randomly to receive treatment with roxadustat in low (1.1–1.8 mg/kg), medium (1.5–2.3 mg/kg) and high (1.7–2.3 mg/kg) doses, or to continue treatment with epoetin alfa.
Epoetin alfa is the generic name of a therapy used to treat anemia in certain patients with CKD. In both studies, patients were allowed to continue taking oral iron supplementation.
The results from this second study showed that 59.1%, 88.9%, and 100% of the patients treated with low-, medium- and high-doses of roxadustat maintained their levels of hemoglobin after five and six weeks of treatment, compared to 50% of the patients who were treated with epoetin alfa.
In both studies, treatment with roxadustat corrected and maintained hemoglobin levels regardless of the patients’ baseline iron repletion status, and levels of C-reactive protein (CRP), a marker of inflammation. Patients treated with roxadustat had significant reductions in hepcidin levels, and their iron levels remained stable or increased. The total iron-binding capacity (TIBC) and transferrin levels rose significantly.
The findings from these Phase 2 trials in China are similar to those observed in other studies from the roxadustat global program.
“Chronic kidney disease is a major chronic health condition in China, and anemia is one of CKD’s most common complications. The publication of this Phase 2 clinical data, along with recently reported Phase 3 primary endpoint data from trials conducted in China, show consistent findings of roxadustat’s potential to treat for dialysis and non-dialysis CKD patients,” said Nan Chen, MD, lead researcher, in a press release. Chen is in the Department of Nephrology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine. “We are gratified to see this demonstration in China of the potential benefits of roxadustat, an oral anemia therapy,” Chen said.
“We are pleased with the positive data that we have seen from our China clinical development program for roxadustat. The published results from our Phase 2 program continue to show that that roxadustat corrects and maintains hemoglobin levels, maintain iron stores, and decreases levels of hepcidin,” said Chris Chung, FibroGen’s Vice President of China Operations.